Assignment of enzyme substrate specificity by principal component analysisof aligned protein sequences: An experimental test using DNA glycosylase homologs

We have studied the relationship between amino acid sequence and substrate specificity in a DNA glycosylase family by characterizing experimentally th e specificity of four new members of the family. We show that principal com ponent analysis (PCA) of the sequence family correctly predicts the substra te specificity of one of the novel homologs even though conventional sequen ce analysis methods fail to group this homolog with other sequences of the same specificity. PCA also suggested, correctly, that another homolog chara cterized previously differs in its specificity from those sequences with wh ich it clusters by conventional criteria. These results suggest that princi pal component analysis of sequence families can be a useful tool in annotat ing genome sequences when there is ambiguity concerning which subfamily a n ew homolog belongs to. Published 2000 Wiley-Liss, Inc.(dagger)